Between 1985 and 1991, approximately 30,000 persons in Linxian, China participated in two nutritional intervention trials that tested whether various mineral and vitamin supplements would decrease the incidence of esophageal and gastric cancer. In 1996, the mortality and morbidity of these participants was assessed by interview, physical examination, and selected endoscopic examinations. During the past year, our international panel of experts completed the review and classification of the pathologic, radiologic, and clinical evidence documenting the cancers and strokes diagnosed since 1991. We verified 1,388 new incident esophageal and gastric cancers, and 1,158 new strokes. We have started to analyze these data and have found that the benefit on total mortality and cancer incidence for those who received the beta-carotene, vitamin E, and selenium still exists five years after the end of the supplementation. Serum studies that we are now completing indicate that persons who started the study with low selenium or low vitamin E, had a significantly higher risk of developing cancer than individuals with higher values. This supports the hypotheses that the benefit we found was and due to the supplementation We have found that serologic evidence of infection with human papilloma virus type 16 and 73 is associated with increased rates of squamous esophageal cancer and adenomatous gastric cardia cancer. No such association appears with the adenomatous gastric cancers that occur in the non-cardia region of the stomach. Preliminary results indicate that serologic evidence of H. pylori infection is associated with increased risk of both cardia and non-cardia gastric cancers. Results from serum measurements on B-vitamins show that the Linxian subjects have markedly high levels of homocysteine (homocysteine is thought to be a cause of stroke and heart disease) and low levels of many B-vitamins : the average homocysteine level in Linxian is nearly twice the level found in the United States;75% of the population was deficient in vitamin B12 Deficiencies of this degree are typically associated with debilitating central and peripheral nervous system deficits, and with profound disruption of hematologic maturation. In April we conducted a study that measures nervous system function and the status of peripheral blood in 1,000 subjects. This study also will enable us to validate and further develop the nutrition questionnaire we use to assess dietary adequacy in our subjects. In addition to the intensive examination of 1,000 subjects, all 23,000 living participants will have blood drawn using procedures that, for the first time, will allow us to measure vitamin C, and to preserve white blood cells as a source of DNA for future genetic studies. We have just completed the third year of our intervention trial in Shandong, China. This is a multi-factorial study that tests whether treatment for Helicobacter pylori (H. pylori), supplementation with vitamin E, vitamin C, and selenium, and supplementation with a garlic extract lowers the prevalence of gastric dysplasia. In the past year, we have published a paper describing the statistical design. Only 52 of 3,411 participants have been lost to follow-up after three years. Over the past 12 months 12 months (April 1998 to April 1999) , the overall average compliance rate for taking the pills was 93%. Among 1,108 H. pylori seropositive subjects who received amoxicillin/omeprazole treatment for two weeks, 708 (64%) were 13C-UBT negative after 3 months following the treatment compared with 142 (13%) among 1,116 H. pylori seropositive subjects who received placebo treatment. Of the 736 subjects who were retreated, 34% of the active group and 6.3% of the placebo group produced negative 13C-UBT results. Combining results from the initial and repeat treatments, the proportion of participants who received active treatment and were 13C-UBT negative was 76% compared to 18% in these given placebo and retreatment with a placebo. We conducted a questionnaire survey to determine the sequella of an outbreak of chronic fatigue syndrome that occurred in Incline Village, Nevada between 1984 and 1987. Our results show that by the end of ten years, only 15% of persons who met the Centers for Disease Control and Prevention criteria for chronic fatigue syndrome had recovered. Recovery was more common (36%) for persons with idiopathic chronic fatigue.